Abstract: :
Purpose:Ischemic retinal diseases such as diabetic retinopathy,retinopathy of prematurity and age-related macular degenerationare a major cause of blindness in the world. HIV vectors areable to achieve long-term gene expression in the non-dividingcells and may be most useful for gene therapy of retinal diseases.We generated an HIV vector encoding angiostatin and examinedthe feasibility of the gene therapy approach to treat retinalneobvascularization in a murine proliferative retinopathy model.Methods:The proliferative retinopathy mouse model was generatedby a sequential exposure of newborn mice to hyperoxia and roomair. The neovascular response was observed in all treated animals.HIV-angiostatin or HIV-EGFP(enhanced green fluorescent protein)as a control was injected into the left vitrous and PBS forright vitrous. The number of retinal neovascular nuclei wasquantified histologically by a masked protocol post HIV injection.Results:HIV mediated gene delivery and expression were confirmedby PCR assay. Histological examination demonstrated that averageretinal neovascular nuclei per 6-µm section in the eyeinjected with HIV-angiostatin was reduced in 90 % (9/10; p=0.025)of animals, compared with the eye injected PBS. No responsewas observed in the eyes injected with HIV-EGFP. Reduction ofneovascular nuclei averaged 68 % with the maximal inhibitoryeffect of 87 %. No apparent inflammatory reaction was observedby light microscopy.Conclusion:This is the first report thatHIV mediated stable expression of angiostatin efficiently reduceretinal neovascularization. These data strongly support thefeasibility of anti-angiostatic gene therapy of ischemic retinaldiseases.